Immunotherapy and tumor mutational burden in cancer patients with liver metastases: A meta and real word cohort analysis

Rui-Yan Wu; Bi-Cheng Wang; Kun Wang; Fan Xia; Zhi-Yuan Zhang; Jue-Feng Wan; Zhen Zhang

doi:10.3389/fonc.2022.994276

Immunotherapy and tumor mutational burden in cancer patients with liver metastases: A meta and real word cohort analysis

Front Oncol. 2023 Jan 19:12:994276. doi: 10.3389/fonc.2022.994276. eCollection 2022.

Authors

Rui-Yan Wu^{1

2

3

4}, Bi-Cheng Wang⁵, Kun Wang^{1

2

3

4}, Fan Xia^{1

2

3

4}, Zhi-Yuan Zhang^{1

2

3

4}, Jue-Feng Wan^{1

2

3

4}, Zhen Zhang^{1

2

3

4}

Affiliations

¹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁴ Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁵ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Background: The predictive effects of liver metastases for immune-checkpoint inhibitors (ICIs) and the relationship between tumor mutational burden (TMB) and liver metastases (LM) remain unclear.

Methods: A systematic review and meta-analysis were conducted to explore the heterogeneity of ICIs efficacy between patients with or without LM. A pan-cancer cohort of 1,661 patients who received ICIs was downloaded and analyzed to assess the association between TMB and LM.

Results: Of 21053 studies identified in our search, eight single-arm studies and 24 randomized controlled trials were included. Overall, 17957 patients with advanced or metastatic cancers (4805 patients (26.8%) with LM and 13151 patients (73.2%) without LM) were enrolled. The pooled objective response rate (ORR) was 8.5% (95% CI 4%-13%) in the LM group versus 21% (95% CI 16%-21%) in the non-LM group. The pooled hazard ratio (HR) for death was 0.85 (95% CI 0.80-0.90) in the LM group treated with ICIs compared with the standard of care. In patients without LM who were treated with ICIs, the pooled HR for death was 0.78 (95% CI 0.73-0.82) compared with the standard of care. The difference in efficacy between patients with or without LM treated with ICIs was significant (p=0.04). Pan-cancer analysis revealed that the TMB-high rate was 10.8% in liver metastatic lesions versus 21.4% in other metastatic lesions (p=0.004). In addition, TMB was also significantly associated with OS as a binary cutoff (p=0.05) and was an independent prognostic variable (HR=0.98, P=0.047) as a continuous variable in patients with LM.

Conclusions: In patients with LM, the efficacy of immunotherapy was attenuated, but TMB-high could predict better survival outcomes.

Keywords: immune-checkpoint inhibitors; immunotherapy; liver metastases; meta - analysis; tumor mutational burden (TMB).

Grants and funding

This study was supported by the National Natural Science Foundation of China (82002905, 82003229), the Shanghai sailing plan (20YF1408300) and Key Clinical Specialty Project of Shanghai.